glycogen and Psoriasis

Topics: Adenylyl Cyclases; Arachidonic Acids; Calmodulin; Cell Division; Cyclic AMP; Cyclic GMP; Epidermis; Glycogen; Glycolysis; History, 20th Century; Homeostasis; Humans; Keratins; Lithium; Phosphorylation; Plasminogen Activators; Polyamines; Propranolol; Psoriasis; Receptors, Cell Surface; Skin

Psoriasis is a chronic, relapsing dermatosis characterised by scaling, erythema, and less commonly pustulation. Although the clinical spectrum is broad and the nature of the underlying defect responsible for the production of psoriasis uncertain, all currently available effective remedies are capable of inhibiting epidermal mitosis and this remains the most widely accepted concept in the management of psoriasis.

Topics: Administration, Topical; Adrenal Cortex Hormones; Age Factors; Anthralin; Ficusin; Glycogen; Hair; Humans; Hydroxyurea; Methotrexate; Mitosis; Mucous Membrane; Nails; Psoriasis; Skin; Tars; Tretinoin; Ultraviolet Therapy

The second messengers cyclic AMP and cyclic GMP in several organs appear to coordinate those molecular events which are responsible for specialized organ function. As a result of balanced cell proliferation and specialization, epidermis functions by terminal specialization which provides a barrier between man and environment. Since the epidermal component of psoriasis is a classic example of deranged epidermal homeostasis, which has a low level of cyclic AMP and a high level of cyclic GMP, it seems reasonable that rebalancing these cyclic nucleotides might ultimately be a safe and effective therapy for psoriasis and other proliferative skin diseases.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenylyl Cyclases; Animals; Cyclic AMP; Cyclic GMP; Glycogen; Growth Inhibitors; Guanylate Cyclase; Homeostasis; Humans; Light; Mice; Mitosis; Protein Kinases; Psoriasis; Rats; Skin; Temperature

Numerous general metabolic systems are disturbed in association with psoriasis: the frequency of diabetes mellitus and of hyperuricaemia, lipid disturbances and a decrease in folates as a result of their excessive consumption by the skin. Cutaneous metabolism is also altered. Numerous compounds are formed in excess from glucose: amino acids, fatty acids and sterols, lactic acid--the formation of which persists in the corneal layer, ribose and ribulose--synthesised as a result of glucose-6-phosphate-dehydrogenase hyperactivity (role of the increased catabolism of dehydro-epi-androsterone) and uronic acids. The accumulation of glycogen is probably due to excessive synthesis and impaired breakdown. These abnormalities may exist to a lesser extent in healthy skin. In the corneal layer there are lipid vacuoles visible under the electron microscope. Lipogenesis is increased. The same may apply to lipolysis (blood NEFA are increased). Esterification of cholesterol is decreased. The utilisation of ATP by cell membranes is probably diminished (low ATP ase activity). The absence of formation of keratohyaline is due to persistence of the repression which normally prevents it in the mucus body. Renewal of collagen appears increased. The synthesis of DNA is increased in the lesions and neighbouring areas. It is possible that these various abnormalities are dependent upon modifications in the regulator systems of cyclic AMP and GMP, variations in which are however discussed.

Topics: Adenosine Triphosphatases; Blood Glucose; Collagen; Cyclic AMP; Cyclic GMP; DNA; Glycogen; Glycolysis; Humans; Keratins; Lipid Metabolism; Metabolic Diseases; Metals; Mitochondria; Oxygen Consumption; Pentosephosphates; Proteins; Psoriasis; Skin

Topics: Adenylyl Cyclases; Animals; Cell Differentiation; Cell Division; Cyclic AMP; Cyclic GMP; Glycogen; Guanylate Cyclase; Histocytochemistry; Humans; Microscopy, Electron; Phentolamine; Phosphoric Diester Hydrolases; Propranolol; Protein Kinases; Psoriasis; Skin

Topics: Adenylyl Cyclases; Animals; Bucladesine; Cell Differentiation; Cell Division; Cyclic AMP; DNA; Epinephrine; Glycogen; Growth Inhibitors; Humans; Isoproterenol; Mitosis; Organ Specificity; Psoriasis; Skin; Theophylline; Time Factors; Wounds and Injuries

Psoriasis is a skin inflammatory disorder that affects 3% of the human population. Although several therapies based on the neutralization of proinflammatory cytokines have been used with relative success, additional treatments are required. The in silico analysis of gene expression data of psoriasis lesional skin and an analysis of vitamin B6 metabolites in the sera of psoriasis patients point to altered vitamin B6 metabolism at both local and systemic levels. Functional studies showed that vitamin B6 vitamers reduced skin neutrophil infiltration, oxidative stress and Nfkb activity in two zebrafish models of skin inflammation. Strikingly, inhibition of glycogen phosphorylase L (Pygl) and glucose-6-phosphate dehydrogenase (G6pd), two vitamin B6-regulated enzymes, alleviated oxidative-stress induced inflammation in zebrafish skin inflammation models. Despite the central role of G6pd in antioxidant defenses, the results of the study demonstrate that glycogen stores and G6pd fuel NADPH oxidase to promote skin inflammation, revealing novel targets for the treatment of skin inflammatory disorders.

Topics: Animals; Animals, Genetically Modified; Anti-Inflammatory Agents; Biopsy; Datasets as Topic; Disease Models, Animal; Gene Expression Profiling; Glucosephosphate Dehydrogenase; Glycogen; Glycogen Phosphorylase, Liver Form; HaCaT Cells; Humans; Intravital Microscopy; NADPH Oxidases; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Psoriasis; Signal Transduction; Skin; Vitamin B 6; Zebrafish; Zebrafish Proteins

To determine whether abnormal activity of a calmodulin-containing enzyme which catalyses phosphorylation reactions may play a pathogenetic role in psoriasis, the presence and activity of phosphorylase kinase (PK) in human epidermis were determined in patients with untreated/active psoriasis (n = 10), treated/resolving psoriasis (n = 10), and non-psoriatic controls (n = 10). Biopsies were taken from involved and uninvolved skin for PK, organic phosphorus, and inorganic phosphate estimation, and light and electron microscopy. The enzyme was present in involved and uninvolved skin of every patient in the study. PK activity (units/mg protein) was significantly higher in active psoriasis than in resolving psoriasis and controls. PK activity correlated directly with organic phosphorus levels, and inversely with the extent of cellular glycogenolysis measured by the depletion of glycogen granules within the keratinocytes. The study demonstrates that PK is present in both psoriatic and normal epidermis, with significantly higher levels in active psoriasis. Furthermore, higher levels of PK activity, glycogenolysis and phosphorylation are associated with increased clinical psoriatic activity. We conclude that PK, a calmodulin-containing enzyme, is involved in regulating calcium-dependent phosphorylation events in human epidermis, and disturbance of its activity may play a key role in the clinical manifestations of psoriasis.

Topics: Cytoplasmic Granules; Cytosol; Glycogen; Humans; Keratinocytes; Male; Phosphorus; Phosphorylase Kinase; Phosphorylation; Psoriasis; Skin

The observation that the glycogen content of epidermis from psoriatic lesions and from regenerating wound epithelium is increased has been confirmed by quantitative estimation. In epidermis from psoriatic lesions, although the proportion of glycogen synthase in the I form is only about 5% of the total and similar to control values, total glycogen synthase activity is increased approximately 4-fold and hence glycogen synthase I activity is increased to the same extent. In contrast, total phosphorylase activity is only slightly increased and, since the proportion of the enzyme in the a form is reduced, phosphorylase a activity is similar to control values. In epidermis from psoriatic lesions, the concentration of UDP-glucose is approximately doubled, and the concentrations of fructose 1,6-bisphosphate and of 6-phosphogluconate are increased approximately 5-fold. It is concluded that rates of glycogen synthesis, of glycolysis and of the pentose phosphate pathway are all enhanced in vivo and in consequence the rate of glucose uptake by psoriatic epidermis must be increased. In the non-involved epidermis of psoriatic patients the glycogen content is within normal limits, and although total glycogen synthase activity is increased the ratio of glycogen synthase I to phosphorylase a is maintained at normal levels by the appropriate phosphorylation of both enzymes. In regenerating wound epithelium in the pig, the changes in enzyme activity and in metabolite concentration closely resemble those found in epithelium from psoriatic lesions except that in wound epithelium the proportion of phosphorylase in the a form is increased relative to normal epithelium.

Topics: Animals; Edetic Acid; Epidermis; Glycogen; Glycogen Synthase; Humans; Phosphorylases; Psoriasis; Regeneration; Sodium Fluoride; Swine

This study was undertaken to assess the amount of glycogen present in psoriasis vulgaris (PV), psoriasis erythrodermica (PE) and psoriasis pustulosa generalisata (PPG) lesions before and after photochemotherapy (PUVA). There were more deposits of glycogen in PPG than in PE and PV. With PUVA treatment, glycogen almost completely disappeared in PV and PE, but traces were still observed in PPG. After treatment, the epidermal layers returned to their normal structure but there was no significant improvement in the dilated and tortuous capillaries in the upper corium.

Topics: Capillaries; Epidermis; Evaluation Studies as Topic; Ficusin; Glycogen; Humans; Photochemotherapy; Psoriasis; Skin

Twelve patients with psoriasis were treated by the topical application of 0.1% isoprenaline sulphate ointment for 10 days. Topical white vaseline was used as a control in three patients with psoriasis. The mean glycogen level was found to be decreased significantly (from 120 +/- s.d. 40 to 58 +/- s.d. 26 mg/100 g of wet weight of involved skin) after topical application of 0.1 isoprenaline sulphate and the scaling also disappeared. Topical application of white vaseline did not produce any significant change in glycogen levels or scaling. The changes after isoprenaline application may have been due to an increase in the ratio of cyclic AMP/cyclic GMP which inhibited cell turnover and increased glycogenolysis.

Topics: Administration, Topical; Glycogen; Humans; Isoproterenol; Psoriasis; Skin

PAS staining was used to assess the glycogen content of clinically normal forearm epidermis in 32 patients with active psoriasis, 30 patients with inactive psoriasis and 40 non-psoriatic subjects. Glycogen accumulation was greater in patients with active than in those with inactive psoriasis. The inactive psoriatics showed significantly less glycogen accumulation than the controls.

Topics: Forearm; Glycogen; Humans; Periodic Acid-Schiff Reaction; Psoriasis; Skin

Topics: Adolescent; Adult; Child; DNA; Energy Metabolism; Glycogen; Humans; Psoriasis; RNA; Skin; Sulfhydryl Compounds

Topics: Animals; Bucladesine; Cell Differentiation; Cell Division; Cells, Cultured; Cyclic AMP; Cyclic GMP; DNA; Glycogen; Humans; Mice; Papaverine; Psoriasis; Skin; Theophylline; Xanthines

Transplantation of involved psoriatic and nonpsoriatic human skin onto congenitally athymic (nude) mice has been performed successfully. Although biopsies at selected intervals demonstrate that the excess glycogen deposition normally seen in psoriasis is no longer consistently present, the psoriatic grafts did retain the usual characteristic histologic differences throughout the life of the animal, up to 11 weeks. This grafting procedure potentially represents a useful method whereby the study of psoriasis can be made in a nonhuman, living system.

Topics: Animals; Biopsy; Glycogen; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Biological; Psoriasis; Skin; Skin Transplantation; Transplantation, Heterologous

Topics: Cyclic AMP; Enzyme Activation; Glucosephosphates; Glycogen; Humans; In Vitro Techniques; NADP; Oxidation-Reduction; Phosphorylases; Psoriasis; Skin

Topics: Adenylyl Cyclases; Animals; Catecholamines; Cell Membrane; Cyclic AMP; Glycogen; Guinea Pigs; Homeostasis; Humans; Kinetics; Phosphoric Diester Hydrolases; Protein Kinases; Psoriasis; Rats; Skin

Topics: Adenylyl Cyclases; Cyclic AMP; Glycogen; Humans; Melanocytes; Neoplasms; Psoriasis; Skin

Topics: Cell Division; Cyclic AMP; Cyclic GMP; DNA; Glycogen; Humans; Organ Size; Proteins; Psoriasis

Topics: Adolescent; Adult; Aged; Female; Glycogen; Humans; Leukocytes; Male; Middle Aged; Psoriasis

Topics: Cytoplasm; Eczema; Glycogen; Histocytochemistry; Humans; Mud Therapy; Neurodermatitis; Neutrophils; Psoriasis; Skin Diseases

Topics: Carbon Isotopes; Glucose; Glucosyltransferases; Glycogen; Glycogen Synthase; Humans; Proteins; Psoriasis; Radioisotopes; Skin; Uridine

Topics: Glycogen; Humans; Methods; Psoriasis; Skin

Topics: Adult; Aged; Cell Differentiation; Cell Division; Chromatography, Ion Exchange; Cyclic AMP; Female; Glycogen; Humans; Male; Microscopy, Electron; Middle Aged; Psoriasis; Skin

Topics: Adenylyl Cyclases; Cyclic AMP; Epinephrine; Glycogen; Histamine; Humans; Isoproterenol; Mitosis; Phosphoric Diester Hydrolases; Phosphotransferases; Propranolol; Psoriasis; Skin

Topics: Collagen; Glycogen; Histocytochemistry; Humans; Psoriasis; Skin

Topics: Basement Membrane; Carcinoma; Dermatology; Diagnosis, Differential; Esterases; Fluorescent Antibody Technique; Glycogen; Histocytochemistry; Humans; Keratins; Keratoacanthoma; Keratosis; Lupus Erythematosus, Discoid; Mast-Cell Sarcoma; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Sweat Glands; Urticaria

Topics: Biopsy; Glucosyltransferases; Glycogen; Histocytochemistry; Humans; Kinetics; Male; Psoriasis; Skin

Topics: Animals; Cell Division; Connective Tissue; Edema; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Keratoacanthoma; Parapsoriasis; Psoriasis; Skin; Sulfhydryl Compounds; Sulfides; Swine

Topics: Carbohydrate Metabolism; Glucose; Glycogen; Hexosephosphates; Histocytochemistry; Humans; In Vitro Techniques; Nucleic Acids; Pentoses; Phosphoric Monoester Hydrolases; Psoriasis; Pyruvates; Skin; Uronic Acids